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Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,1David. E. Sleat,12Henry Lackland,1Anthony Fensom,3Marie T. Vanier,4Robert Wattiaux,5Michel Jadot,5Peter Lobel12*
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder
of unknown etiology characterized by defective egressof cholesterol
from lysosomes. Here we show that the disease iscaused by a deficiency
in HE1, a ubiquitously expressed lysosomalprotein identified
previously as a cholesterol-binding protein.HE1 was undetectable in
fibroblasts from NP-C2 patients but presentin fibroblasts from
unaffected controls and NP-C1 patients. Mutationsin the HE1
gene, which maps to chromosome 14q24.3, were foundin NP-C2 patients
but not in controls. Treatment of NP-C2 fibroblastswith exogenous
recombinant HE1 protein ameliorated lysosomal accumulationof low
density lipoprotein-derived cholesterol.
1 Center for Advanced Biotechnology and
Medicine,
2 Department of Pharmacology, University
of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical
School, Piscataway, NJ, 08854, USA.
3 Division of
Medical and Molecular Genetics, the Guy's, King's and St. Thomas'
School of Medicine, Guy's Hospital, London, UK.
4 INSERM 189, Lyon-Sud Medical School, Oullins,
France, and Fondation Gillet-Mérieux, Lyon-Sud Hospital,
Pierre-Bénite, France.
5 Laboratory of
Physiological Chemistry, Facultés Universitaires Notre-Dame de la
Paix, B-5000 Namur, Belgium.
*
To whom correspondence should be addressed. E-mail:
lobel{at}cabm.rutgers.edu
The editors suggest the following Related Resources on Science sites:
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